Cows and rats are highly susceptible to urinary bladder carcinogenesis by bracken fern. Milk obtained from cows ingesting bracken fern contains toxic and carcinogenic metabolites not normally present in cows milk. Human ingesting such milk might be unwittingly exposed to a naturally occurring plant carcinogen. Toxic and carcinogenic metabolites in cow milk and in rat urine will be identified and tested for carcinogenic activity utilizing animal and microbiological systems. The possible role of intestinal bacteria in the metabolic activation of the bracken fern carcinogen will be studied in germ-free rats. Carcinogenic tannin isolated from bracken fern will be tested for carcinogenicity in rodents via different route of administration. An attempt will be made to inhibit carcinogenicity of this plant by adding phenolic antioxidants, sulfur containig substances, calcium salts and nonionic polymers to bracken fern containing diets fed to rats. The proposed studies are designed to meet the specific study objectives outlined in the Experimental Biology Subflow Phase II-1/1-A, Phase II-2.2-A and Phase II-2.2-B of the National Bladder Cancer Project. DTX* 1CA-16329-3*